Cardioprotective effect of acute intradialytic exercise: a comprehensive speckle-tracking echocardiography analysis

Cardiovascular disease remains the leading cause of morbidity and mortality for people with end-stage kidney disease. This is driven by clustering of traditional and disease-specific risk factors, and for patients on haemodialysis the processes of dialysis, particularly large-volume ultrafiltration, drive disease processes directly. During dialysis, as fluid is removed through ultrafiltration, blood volume, and consequently left-ventricular end-diastolic volume, reduces. This reduction in left-ventricular filling reduces stroke volume (remember Starling’s law of the heart?) and, to maintain cardiac output, heart rate has to increase, assuming systemic vascular resistance is unchanged (which sometimes it is not). As heart rate increases, diastole shortens, reducing coronary filling time and oxygen supply to the myocardium. This leads to demand ischaemia. A series of elegant studies in the UK from the late noughties beautifully demonstrated that these ischaemic events manifest as regional wall motion abnormalities that associate with acute myocardial injury, development of fixed regional wall abnormalities, progressive myocardial fibrosis and mortality.[1,2] Crucially, the most important determinant in the development of these myocardial stunning events is volume (or more importantly speed) of ultrafiltration, and can be mitigated by dialysis strategies that reduce ultrafiltration speeds.[3] 

Exercise, or more specifically exercise during dialysis, has been proposed as an alternative way of maintaining cardiovascular health for patients on dialysis. The CYCLE-HD study (for which I was lead author) was a randomised trial that showed a 6-month structured programme of progressive cycling during dialysis improved left-ventricular characteristics, reducing left-ventricular mass and mass/volume ratio, and improved measures of myocardial fibrosis.[4] The mechanisms that drove these improvements in left-ventricular phenotype were not clear, however, so it was with great interest that I read the study by Josse and colleagues. 

The study (published in the Journal of the American Society of Nephrology) reports initial pilot data from the EX-CHRODIAL study, which is investigating the long-term effects of intra-dialytic exercise on long-term cardiovascular health and well-being. The study has a cross-over design in which all patients participated in two haemodialysis sessions in a random order: a standard session and a session with 30 minutes of aerobic exercise – in this case cycling. During the sessions, a transthoracic echocardiogram was performed and standard left-ventricular geometry was acquired, as well as global and regional longitudinal and circumferential systolic strain (a measure of myocardial deformation and an early marker of systolic dysfunction). 60 participants completed the study, which seems to show that cycling during dialysis attenuates decline in global longitudinal strain compared to a standard session of dialysis. Exercise was conducted after 30 minutes of dialysis, with ECHO measures taken before the session started, 90 minutes into the dialysis session and 30 minutes before the end of dialysis. Global longitudinal strain measures were similar prior to the sessions and, although they declined over the course of dialysis when patients exercised and when they did not, the magnitude of decline in the exercise group was reduced and the effect was sustained over the course of the dialysis session.

This is a nice study which replicates the findings of McGuire and colleagues, who showed regional wall motion abnormalities were mitigated by intra-dialytic cycling [5] but, unlike this study and CYCLE-HD, the present study by Josse and colleagues excluded participants with an ejection fraction of <45%, perhaps limiting the generalisability of findings. Nevertheless, this is yet more grist to the mill that exercising during dialysis is safe and does not worsen (and perhaps abrogates) the effects of demand ischaemia from dialysis and ultrafiltration. It offers further insight into the mechanisms that may have led to the beneficial cardiovascular adaptations seen in CYCLE-HD, and it is certain that a great deal more can be expected from the EX-CHRODIAL study, the results of which we look forward to reporting.

A digest of the study can be read here.

References

1. Burton JO, Jefferies HJ, Selby NM, McIntyre CW (2009) Hemodialysis-induced cardiac injury: determinants and associated outcomes. Clin J Am Soc Nephrol 4: 914–20
2. Burton JO, Jefferies HJ, Selby NM, McIntyre CW (2009) Hemodialysis-induced repetitive myocardial injury results in global and segmental reduction in systolic cardiac function. Clin J Am Soc Nephrol 4: 1925–31
3. Jefferies HJ, Virk B, Schiller B et al (2011) Frequent hemodialysis schedules are associated with reduced levels of dialysis-induced cardiac injury (myocardial stunning). Clin J Am Soc Nephrol 6: 1326–32
4. Graham-Brown MPM, March DS, Young R et al (2021) A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass. Kidney Int 99: 1478-86
5. McGuire S, Horton EJ, Renshaw D et al (2019) Cardiac stunning during haemodialysis: the therapeutic effect of intra-dialytic exercise. Clin Kidney J 14: 1335–44